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通过Sonic hedgehog信号,GRP78通过调节骨微环境来促进前列腺癌的骨转移
Minsheng Yang1,2, Kangqiang Weng1,3, Yuanqing Guo2
1Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
Molecular carcinogenesis
|December 12, 2023
概括
葡萄糖调节蛋白 (GRP78) 通过激活Sonic hedgehog (Shh) 途径促进前列腺癌骨转移,驱动骨质细胞和骨质细胞分化. 向GRP78/Shh为晚期前列腺癌提供了一个治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 骨转移是前列腺癌 (PCa) 患者死亡的主要原因.
- 控制PCa对骨微环境的影响的复杂分子机制尚未完全理解.
- 了解这些相互作用对于开发有效的治疗方法至关重要.
研究的目的:
- 研究葡萄糖调节蛋白 (GRP78) 在前列腺癌骨转移和生长中的作用.
- 为了阐明参与GRP78介导的骨微环境调节的分子途径.
- 评估针对GRP78/Shh轴的治疗潜力.
主要方法:
- 为PCa骨转移建立心内和内注射模型.
- 组织学染色,细胞共同培养,ELISA,阿利沙林红色和TRAP染色.
- 在体外和体内评估PCa细胞迁移,入侵和瘤生长.
主要成果:
- GRP78在PCa组织中被上调,与疾病进展相关.
- 过度表达GRP78增强了PCa骨转移,并改变了骨的微观结构.
- 沉默GRP78抑制PCa细胞迁移,入侵和骨转移.
- GRP78通过Sonic hedgehog (Shh) 信号通路促进骨质细胞和骨质细胞分化.
结论:
- GRP78通过激活膜Shh信号来促进PCa骨转移,该信号调节骨质细胞和骨质细胞分化.
- GRP78/Shh轴代表了对抗前列腺癌骨转移的有希望的治疗标.
- 针对这种途径可以改善患者的治疗结果和生活质量.
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